Is There Such A Thing As “Pure” Autism?

Genetic
analysis from a new study in Biological Psychiatry says no

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Philadelphia, PA, April 20, 2015

The search for genes that
contribute to the risk for autism has made tremendous strides over the past 3
years. As this field has advanced, investigators have wondered whether the
diversity of clinical features across patients with autism reflects heterogeneous
sources of genetic risk.

If so, it was reasoned, then
selecting a group of patients with very similar clinical features might result
in a “purer”, i.e., more genetically homogenous, group of patients, making it
easier to find autism-related genes.

Results from a new study published
in the current issue of Biological
Psychiatry now cast the validity of this view into doubt.

A large group of collaborating
scientists used data from the Simons Simplex Collection, a project that
extensively characterized 2576 autism simplex families, the largest such cohort
amassed to date and for which the data is now available in a permanent
repository.

The availability of this
vast collection allowed the researchers to create phenotypic subgroups. In
addition to the whole sample, this resulted in 11 subgroups of patients with
similar diagnostic, IQ and symptom profiles. They then analyzed the genotypic
data in an attempt to discover common genetic variants that confer risk for
autism spectrum disorder.

Their results did not
identify any genome-wide significant associations in the overall sample or in
the phenotypic subgroups. This means that the extreme clinical variability
observed among patients with autism spectrum disorder does not closely reflect
common genetic variation.

“This study did not provide
good evidence that selecting patients with similar symptoms results in a
greater ability to find autism genes,” said Dr. John Krystal, Editor of Biological Psychiatry. “This might
suggest that some of the clinical variability in autism arises from causes
other than genetic vulnerability, such as epigenetic changes or other responses
to the environment.”

It is
important to note that these results are in alignment with the recent major
change to autism’s diagnostic classification in the Diagnostic and Statistical Manual of Mental Disorders. In its 5th
revision, several separate disorders, which included autism and Asperger’s
disorder, were grouped into a single category termed autism spectrum disorder.
That decision was based on growing evidence that the previously-distinct
disorders actually reflected a continuum of severity of the same condition.

“We
hope our study is a step towards a new paradigm for studies involving the
relationship between psychiatric phenotypes and genotypes. Most previous
studies have sought to refine or narrow phenotypic variation irrespective of
its impact on genetic variation, with the expectation that such refinement will
improve detection of genetic variation increasing risk for a disorder,”
explained first author Dr. Pauline Chaste from Centre Hospitalier Sainte Anne
in France.

“Our
results motivate another route, one targeting the genetic structure of traits
and, for multiple traits, their genetic correlations,” Chaste added. “For
autism, one important implication of our results is that our colleagues have
done a very good job in first defining it; however, to make better headway on
discovering genetic variation underlying risk, we believe refining phenotypes
in light of their impact on genetic architecture will be essential.”

Notes for editorsFull text of the article is available to credentialed journalists
upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu. Journalists
wishing to interview the authors may contact Dr. Pauline Chaste at +33-1-45-65-61-05
or p.chaste@ch-sainte-anne.fr.

The
authors’ affiliations, and disclosures of financial and conflicts of interests
are available in the article.

John
H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale
University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital,
and a research psychiatrist at the VA Connecticut Healthcare System. His
disclosures of financial and conflicts of interests are available here.

About
Biological PsychiatryBiological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote
excellence in scientific research and education in fields that investigate the
nature, causes, mechanisms and treatments of disorders of thought, emotion, or
behavior. In accord with this mission, this peer-reviewed, rapid-publication,
international journal publishes both basic and clinical contributions from all
disciplines and research areas relevant to the pathophysiology and treatment of
major psychiatric disorders.

The journal publishes novel results of original research
which represent an important new lead or significant impact on the field,
particularly those addressing genetic and environmental risk factors, neural
circuitry and neurochemistry, and important new therapeutic approaches. Reviews
and commentaries that focus on topics of current research and interest are also
encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in
the field of psychiatric neuroscience.
It is ranked 5th out of 135 Psychiatry titles and 14th
out of 251 Neurosciences titles in the Journal Citations Reports® published by
Thomson Reuters. The 2013 Impact Factor score for Biological Psychiatry
is 9.472.

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